Weeks Research Articles

Hyperglycemia-Driven Insulin Signaling Defects Promote Parkinson's Disease-like Pathology in Mice.

This study aims to determine the effect of chronic hyperglycemia, induced by a high-fat diet and STZ-induced diabetes, on the development of Parkinson's disease-like characteristics. Understanding this relationship is crucial in pharmacology, neurology, and diabetes, as it could potentially lead to developing new therapeutic strategies for Parkinson's disease. Our study employed a comprehensive approach to investigate the effect of hyperglycemia on Parkinson's disease-like characteristics. Hyperglycemia was induced by a high-fat diet for 6- and 9-week duration with a single intraperitoneal STZ (100 mg/kg) injection at week 5 in C57/BL6 mice. Rotenone (10 mg/kg p.o.) was administered to C57/BL6 mice for 6 and 9 weeks. Time-dependent behavioral studies (wire-hang tests, pole tests, Y-maze tests, and round beam walk tests) were carried out to monitor pathology progression and deficits. Molecular protein levels (GLP1, PI3K, AKT, GSK-3β, NF-κB, and α-syn), oxidative stress (GSH and MDA) parameters, and histopathological alterations (H&E and Nissl staining) were determined after 6 weeks as well as 9 weeks. After 9 weeks of study, molecular protein expression (p-AKT and p-α-syn) was determined. Hyperglycemia induced by HFD and STZ induced significant motor impairment in mice, correlated with the rotenone group. Insulin receptor signaling (GLP1/PI3K/AKT) was found to be disrupted in the HFD+STZ group and also in rotenone-treated mice, which further enhanced phosphorylation of α-syn, suggesting its role in α-syn accumulation. Histopathological alterations indicating neuroinflammation and neurodegeneration were quite evident in the HFD+STZ and rotenone groups. Exposure to hyperglycemia induced by HFD+STZ administration exhibits PD-like characteristics after 9 weeks of duration, which was correlative with rotenone-induced PD-like symptoms.

Navigating diagnostic dilemmas: a rare presentation of extramedullary T-lymphoblastic leukemia/lymphoma with chronic myeloid leukemia.

Chronic myeloid leukemia (CML) typically presents in the chronic phase. The blast crisis phase in CML predominantly comprises the myeloid phenotype, while B-cell lymphoblastic crisis is common among the lymphoid lineages. Presentation as a T-lymphoblastic crisis is exceptionally rare. Little is known about its characteristics, treatment, and prognosis. This case study reports a patient who presented as an extramedullary blast crisis with T-lymphoblastic immunophenotype without a known prior diagnosis of CML. We performed hematoxylin and eosin staining, immunohistochemistry on the inguinal lymph node, and bone marrow biopsy. Ancillary studies including flow cytometry and cytogenetic testing were conducted as needed. BCR::ABL1 is quantitative real-time polymerase chain reaction monitored disease progression. Our patient is a 40-year-old male with no previous medical history who presented with neck stiffness and pain of one week in duration. Clinical evaluation revealed diffuse lymphadenopathy and splenomegaly. A biopsy from the inguinal lymph node revealed T-lymphoblastic lymphoma (T-LBL) (90%) and a population of myeloblasts (10%). Subsequent bone marrow biopsy showed myelocyte expansion, dwarf megakaryocytes, scattered myeloblasts (9%), and T-lymphoblasts (6%). Flow cytometry of the bone marrow aspirate revealed myeloblasts (5.4%) and T-lymphoblasts (6.3%). Genetic and molecular studies identified the BCR-ABL1 fusion. This case contributes to the medical literature by documenting a rare occurrence of extramedullary T-LBL with concurrent CML. The absence of a CML history makes the diagnosis particularly challenging and underscores the need for comprehensive and personalized treatment strategies.

Results of a Phase 2 Multicenter Study to Evaluate the Efficacy of VP-315, an Investigational Therapy for Basal Cell Carcinoma

Introduction: VP-315 is an intratumorally injected, chemotherapeutic oncolytic peptide in development as a non-surgical immunotherapeutic agent to be utilized as first line therapy in a primary or neoadjuvant setting for patients with basal cell carcinoma (BCC). Objective: In Part 2 of this study, the secondary objective was to evaluate the effect of various dosing regimens on the antitumor efficacy of VP-315 in a larger population of adult subjects with biopsy proven BCC. Methods: Eighty-two (82) subjects with up to 2 target BCC tumors (total 91 tumors) were treated intratumorally with VP-315 for up to 2 weeks. Cohort 3 was not enrolled based on results from Cohorts 1-2. Each 7-day treatment week was comprised of 2 or 3 consecutive treatment days followed by a no-treatment period of at least 4 days. Dosing scheme: Cohort 1: (n=6) Tumor injected 3 days consecutively (3X/week 4 mg loading dose Day 1 followed by 8 mg dose). Cohort 2: (n=3) Tumor injected 3 days consecutively (3X/week 8 mg dose). Cohort 4: (n=36) Each tumor was injected 2 days consecutively (2X/week 8 mg split dose*). Cohort 5: (n=37) Each tumor was injected 3 days consecutively (3X/week 8 mg split dose*). * Dose split into 2 injections, 30% injected initially; 70% injected 15-30 minutes later. Efficacy endpoints included histological clearance of target tumor(s) and estimate of remaining tumor volume (tumor size reduction) at excision (Week 12-13). Results: Eighty-two (82) subjects (n=92 lesions) completed treatment for BCC with VP-315 in Part 2. Approximately 51% of tumors achieved complete histologic clearance. All tumors treated had a reduction in tumor size. Overall tumor size reduction was 86%. Tumor size reduction in subjects who still had any residual tumor was 71%. Conclusion: Complete histological clearance in a majority of VP-315 treated tumors could eliminate the need for surgical intervention in those patients in clinical practice. In subjects with residual tumor burden, the substantial reduction in tumor size after VP-315 treatment would markedly reduce the surgical incision area and the amount of potential post-surgical scarring. Based on the favorable results, further research using VP-315 as a potential non-surgical immunotherapy for BCC as a first line therapy in a primary or neoadjuvant setting is warranted.

Results of a Phase 2 Multicenter Study Evaluating the Safety and Tolerability of VP-315, an Investigational Therapy for Basal Cell Carcinoma

Introduction VP-315 is an intratumorally injected, chemotherapeutic oncolytic peptide in development as a non-surgical immunotherapeutic agent to be utilized as first line therapy in a primary or neoadjuvant setting for patients with basal cell carcinoma (BCC). Objective In Part 2 of this study, the primary objective was to determine the optimal dosing regimen for VP-315 by exploring the effects of various dosing schemes on the safety and tolerability of VP-315 in a larger population of subjects with biopsy proven BCC. Methods Eighty-two (82) subjects with up to 2 target BCC tumors (total 91 tumors) were treated intratumorally with VP-315 for up to 2 weeks. Cohort 3 was not enrolled based on results from Cohorts 1-2. Each 7-day treatment week was comprised of 2 or 3 consecutive treatment days followed by a no-treatment period of at least 4 days. Dosing scheme: Cohort 1: (n=6) Tumor injected 3 days consecutively (3X/week 4 mg loading dose Day 1 followed by 8 mg dose). Cohort 2: (n=3) Tumor injected 3 days consecutively (3X/week 8 mg dose). Cohort 4: (n=36) Each tumor was injected 2 days consecutively (2X/week 8 mg split dose*). Cohort 5: (n=37) Each tumor was injected 3 days consecutively (3X/week 8 mg split dose*). * Dose split into 2 injections, 30% injected initially; 70% injected 15-30 minutes later. Safety and tolerability were assessed by documenting the occurrence of Treatment Related Adverse Events (TRAEs), including those of special interest, Treatment Related Serious Adverse Events (TRSAEs), discontinuations due to AEs and expected treatment-related cutaneous reactions including tumor necrosis. Results All 82 subjects completed one of the VP-315 treatment regimens for BCC. TRAEs were mostly mild to moderate. AEs included injection site pain (mild 13.4%, moderate 12.2%, severe 1.2%), hypertension (mild 4.9%), hypotension (mild 4.9%), erythema (mild 1.2%, moderate 2.4%), and headache (mild 2.4%). Expected cutaneous reactions were observed. No TRSAEs were reported. Conclusion VP-315 treatment was shown to be safe and well-tolerated when administered once daily 2-3 times per week per tumor for up to 2 weeks using a split dose approach. Given its favorable safety profile, VP-315 warrants continued research as a potential non-surgical immunotherapy for BCC as a first line therapy in a primary or neoadjuvant setting. Sponsored by Verrica Pharmaceuticals Inc.

Impact of remote social interaction during the COVID-19 pandemic on the cognitive and psychological status of older adults with and without cognitive impairment: A randomized controlled study.

Social isolation and loneliness have both been associated with psychological health and cognitive decline in older adults. This study investigated the impact of social interaction through remote communication technologies during the COVID-19 pandemic on the cognitive and psychological status of older adults with and without cognitive impairment. Participants were recruited from Boston (USA) and Chieti (Italy). The study used a randomized single-blinded controlled crossover design with an intervention (remote social conversations with research staff over 20-minute video or telephone calls three times per week) and a passive control condition, each one of 4-weeks duration. The primary outcome was a composite cognitive score change from baseline to week 4. Secondary outcomes included scales for mood, anxiety, and loneliness. Out of 196 participants recruited from April 2020 to April 2021, 17% dropped out. Based on the blind MoCA, 52% had cognitive impairment, and 25% were at risk of social isolation according to the Lubben social network scale. We observed that larger social networks were linked to better cognitive status and lower depression and anxiety levels, while loneliness was directly associated to depression severity. Older adults with cognitive impairment exhibited higher levels of depression and anxiety and were at greater risk for social isolation. In terms of the intervention, 91% preferred telephone over video calls. The intervention did not lead to improvements in cognitive or psychological scores. More work is needed to assess the utility of this intervention for the support of a heterogenous cross-cultural sample of older adults at-risk for social isolation, including individuals with cognitive impairment. Future research should explore longer intervention periods, categorize participants by call type, and target those meeting social isolation criteria. ClinicalTrials.gov NCT04480112.

Risk of Anterior Cruciate Ligament Tears in National Football League Players by Short, Normal, or Long Rest Weeks.

Anterior cruciate ligament (ACL) tears in National Football League (NFL) players are devastating injuries that take nearly a year to recover. Players that do return to sport have worse overall performance compared to pre-ACL tear. NFL players typically play regular season games on Sunday with the next game played on the following Sunday, allowing for 6 days between games. Deviation from the usual 6-day rest week has been proposed as a potential risk for ACL tear. The main objective of this study was to evaluate the risk of decreased rest or increased rest on ACL tear rates in NFL players. ACL injury data of NFL players from the 2012 to 2013 season and 2022 to 2023 season were gathered from publicly available sources. Player demographic data, position, age at time of injury, seasons played, injury mechanism, and playing surface type were recorded. Injuries were characterized as short, normal, or long week injuries. ACL tears that occurred during the preseason, postseason, or during week 1 were excluded. Descriptive statistics were calculated to report means, ranges, and percentages. Data were analyzed to determine statistically significant differences using Fisher's exact, chi-square, or one-way analysis of variance tests. A total of 524 ACL tears were recorded in NFL players during the study window. Note that 304 ACL tears were excluded and 220 fit inclusion criteria. Twenty-four ACL tears occurred during short weeks, 68 during long weeks, and 128 during normal weeks. Players were 1.8 times more likely to tear their ACL during a long week compared to a normal week (p < 0.001), and 1.5 times more likely to tear their ACL during a short week compared to a normal week (p = 0.02). The findings from this study suggest that deviation from the normal 7-day NFL week increases the risk of an ACL tear in NFL players when increasing or decreasing rest time. Further research exploring the impact of short and long rest times on player injury risk should be conducted to prevent season-ending injuries.

Mammary Carcinoma Metastasizing to Renal Cell Carcinoma: A Case Report

Abstract Introduction/Objective The simultaneous occurrence of multiple primary cancers is rare, and even rarer is the phenomenon of one cancer metastasizing to another. Here, we present a case of mammary carcinoma and renal cell carcinoma diagnosed concurrently yet presenting as a cancer-to-cancer metastasis. Methods/Case Report A 79-year-old woman, with a 2-week duration of apnea and cough, was found to have right pleural effusion and underwent thoracocentesis. Cytological examination of the fluid revealed malignant cells suggestive of adenocarcinoma. CT abdomen and chest revealed a 1.6 cm right breast nodule, 4.4 cm right axillary mass and right renal lesions measuring 3.0 and 1.6 cm. Core biopsy of the renal lesion showed two populations of cells. One population exhibited moderate cytoplasm and enlarged nuclei displaying anisonucleosis and hyperchromasia arranged singly as well as in sheets and clusters. These cells stained positive for GATA 3, ER, mammaglobin and CK7. Intermixed, were the second population of cells with clear cytoplasm and low nuclear grade forming sheets and replacing renal tissue. These cells were positive for CA9, CD10 and PAX 8 but negative for P40. Based on these findings a diagnosis of low-grade renal carcinoma of clear cell type with a metastatic carcinoma of mammary origin was established. Results (if a Case Study enter NA) NA Conclusion Renal cell carcinoma and breast carcinoma are known to increase the occurrence of each other. When breast and renal lesions are identified concurrently, the possibility of breast metastasis should be strongly considered. However, the concurrent appearance of renal cell carcinoma harboring metastatic breast cancer is extremely rare.This contributes valuable insights into the complex interplay between different cancer types. Understanding these rare phenomena can aid in refining diagnostic approaches and treatment strategies.

Clinical course and radiographic resolution of pneumonia in dogs treated with a shorter versus longer course of antimicrobials: a randomized, double-masked, placebo-controlled study.

To describe clinical and radiographic outcomes in dogs with uncomplicated pneumonia receiving a shorter (2-week) versus longer (4-week) duration of antimicrobial therapy. 30 client-owned dogs with radiographic evidence of pneumonia. Dogs were randomly assigned to either a 2-week course of antimicrobials followed by a 2-week course of placebo medication (2-week group) or a 4-week course of antimicrobials (4-week group). All study investigators and owners were masked to the treatment group. Dogs were reevaluated at 12 ± 2 days and again at 28 ± 2 days for a physical examination and thoracic radiography. Standard documentation at visits included owner-reported clinical signs, nurse-acquired history, the clinician's physical examination, the number of affected lung lobe segments, and the global radiographic severity scores assigned. Outcomes investigated included the persistence of clinical and radiographic signs of pneumonia. 28 dogs (93.3%) experienced complete resolution of clinical signs by the first visit, and no dogs in either group experienced relapse of clinical signs during the study period. Eighteen of 30 dogs (60%) and 25 of 30 dogs (83%) experienced complete resolution of radiographic lesions at the first and second study visits, respectively. The remaining 5 dogs (17%) had either stable (4 dogs) or continued (1 dog) improvement in radiographic lesions. Resolution of clinical and radiographic signs followed similar courses in dogs with uncomplicated pneumonia receiving a 2-week course of antimicrobials compared to a 4-week course. Clinical signs may be more useful for guiding discontinuation of antimicrobial therapy for pneumonia than radiographic signs.

275 Frequency of chronic passive congestive livers at harvest in the Texas Panhandle and the association with carcass outcomes

Abstract Chronic passive congestive (CPC) livers are reported as one of the most common clinical signs of right-sided Bovine Congestive Heart Failure (BCHF). Frequency of CPC livers at harvest and the associated loss of offal and carcass value does not appear in the literature. Our objectives were to 1) quantify the frequency of CPC livers at harvest within the Texas Panhandle, and 2) evaluate the association with offal and carcass outcomes. Audits were performed over the duration of a production week (both harvest shifts) per each large commercial beef processing facility (4 total) in the Texas Panhandle. West Texas A&amp;M University trained personnel identified CPC (large blue) livers at evisceration and documented heart score (HS; scale 1 = normal to 5 = extreme structural changes), liver weight, USDA-FSIS inspection fate (U.S. Inspected &amp; Passed; U.S. Condemned) of the liver, remaining viscera, and carcass. Other visual observations (sex, predominant black hair coat color, carcass/visceral edema, liver abscesses) were noted. 1) Frequency data were documented among cattle-type populations: sex (steers, heifers, cows, bulls), and phenotype [native, dairy-cross, dairy, category-B (Mexico-origin)]. 2) Carcass and lot identification were collected for the purpose of tracking and obtaining carcass grading data. Of carcasses deemed wholesome-U.S. Inspected &amp; Passed, USDA yield and quality metrics [hot carcass weight (HCW), 12th-rib fat thickness (FT), ribeye area (REA), marbling score (MS)] of those identified with CPC, as well as data for the balance of respective lots were collected. Carcass outcomes of those exhibiting a CPC liver were compared with the outcomes of remaining lot. Frequency data were analyzed via chi-square. Carcass data were analyzed using mixed models, where occurrence of CPC liver was the fixed effect; facility, cattle type, and sex were random effects. A total of 83,527 animals were audited, with a CPC liver frequency of 0.17% (n = 144). Frequencies among sex (steer = 0.16%; heifer = 0.17%; cow = 0.33%; P &amp;lt; 0.01) and phenotypes (native = 0.15%; category-B = 0.04%; dairy cross = 0.14%; P = 0.01) were documented. Heart scores ranged from 1 to 4, with HS 3 occurring most frequently [HS 1 (n = 2); HS 2 (n = 39); HS 3 (n = 62); HS 4 (n = 17)]. Weights of CPC livers ranged from 7.3 kg to 34.4 kg; the heaviest CPC livers were recorded in cows (mean = 17.2 kg; P &amp;lt; 0.01). Despite USDA-FSIS guidelines, 2.08% of CPC livers were U.S. Inspected &amp; Passed, along with 16.90% of viscera and 84.03% of carcasses. Cow carcasses encountered the greatest U.S. Condemn-rates (38.24%) among the sex categories. Within the fed-beef population, natives were the only category resulting in U.S. Condemned carcasses (10.64%). All carcass outcomes were decreased (P ≤ 0.01) by CPC livers.

Risk of SARS-CoV-2 infection in professional settings, shops, shared transport, and leisure activities in France, 2020–2022

PurposeThe aim of the study was to identify settings associated with SARS-CoV-2 transmission throughout the COVID-19 pandemic in France.MethodsCases with recent SARS-CoV-2 infection were matched with controls (4:1 ratio) on age, sex, region, population size, and calendar week. Odds ratios for SARS-CoV-2 infection were estimated for nine periods in models adjusting for socio-demographic characteristics, health status, COVID-19 vaccine, and past infection.ResultsBetween October 27, 2020 and October 2, 2022, 175,688 cases were matched with 43,922 controls. An increased risk of infection was documented throughout the study for open-space offices compared to offices without open space (OR range across the nine periods: 1.12 to 1.57) and long-distance trains (1.25 to 1.88), and during most of the study for convenience stores (OR range in the periods with increased risk: 1.15 to 1.44), take-away delivery (1.07 to 1.28), car-pooling with relatives (1.09 to 1.68), taxis (1.08 to 1.89), airplanes (1.20 to 1.78), concerts (1.31 to 2.09) and night-clubs (1.45 to 2.95). No increase in transmission was associated with short-distance shared transport, car-pooling booked over platforms, markets, supermarkets and malls, hairdressers, museums, movie theatres, outdoor sports, and swimming pools. The increased risk of infection in bars and restaurants was no longer present in restaurants after reopening in June 2021. It persisted in bars only among those aged under 40 years.ConclusionClosed settings in which people are less likely to wear masks were most affected by SARS-CoV-2 transmission and should be the focus of air quality improvement.ClinicalTrials.gov (03/09/2022)NCT04607941.

Abstract P301: A Meta-Analysis of Randomized Controlled Trials: Aldosterone Synthase Inhibitors as a Therapeutic Strategy for Hypertension

Introduction: Hypertension is a widespread health concern globally, often associated with excessive aldosterone production. Aldosterone synthase inhibitors (ASIs) have been proposed as potential therapeutic agents. Yet, their effectiveness and safety in managing blood pressure in hypertensive adults are not definitively established. This study aims to elucidate this matter through a comprehensive systematic review and meta-analysis of Randomized Controlled Trials (RCTs). Hypothesis: We hypothesize that ASIs could be a safe and effective strategy for managing blood pressure in adults diagnosed with hypertension. Methods: A systematic review and meta-analysis of seven RCTs were conducted to assess the impact of ASIs versus placebo in hypertensive patients. The studies were systematically sourced from MEDLINE and EMBASE until March 30 th , 2024. Continuous outcomes were pooled using the mean difference (MD), and dichotomous outcomes were pooled using the risk ratio (RR), both with their respective confidence intervals (CI). Results: Our meta-analysis incorporated data from seven randomized studies, averaging 7.7 ± 2.4 weeks in duration, and involving a total of 1440 patients. Compared to placebo, ASIs showed effectiveness in controlling systolic blood pressure (MD: -6.12 mm Hg; 95% CI [−4.32, −7.92]; p &lt; 0.0001; I 2 = 0%) and diastolic blood pressure (MD: −2.71; 95% CI [−1.07, −4.36]; p = 0.001; I 2 = 0%). Notably, the incidence of adverse events did not significantly differ from that observed with placebo (RR: 1.11; 95% CI 0.95 to 1.29; p = 0.18; I 2 = 0%). Conclusions: Our findings suggest that ASIs could be a safe and effective approach for managing blood pressure in hypertensive adults, with no significant difference in the incidence of adverse events compared to placebo. These results advocate for further investigation of ASIs in larger, long-term trials to confirm their safety and efficacy, and to explore any additional therapeutic benefits over mineralocorticoid receptor antagonists. Future research should also thoroughly examine the potential benefits of these inhibitors in diverse patient populations, including those with obesity-associated hypertension and suppressed plasma renin activity.

Electronic Prescribing by Medical Students: Descriptive Data and Inferred Clinical Impact.

We analysed data from the electronic medication chart at tertiary healthcare facilities during Nov 2020-Nov 2023 following a reconfiguration of prescribing permissions allowing medical student inpatient prescribing. A total of 262 students prescribed for 2205 patients. The 17,769 prescriptions were spread throughout the 7-day week and were mainly created in the evening (1600-2100) and within 4 hours of patient entry into hospital. The supervising doctors approved 11,434 (64%) prescriptions, which are inferred to have saved 203 hours of doctor time. Allowing medical students to prescribe facilitates clinical workflow. The impact on student education and prescribing errors requires further work.

Baduanjin exercise for negative emotion of patients undergoing chemotherapy: a systematic review and meta-analysis.

Baduanjin was also called Eight Brocades (EB), a branch of Qigong exercise, is classified as a mild-to-moderate intensity aerobic exercise. It has been theorized that regular practice of EB can alleviate anxiety and depression in patients undergoing chemotherapy; however, there are currently no comprehensive quantitative reviews on the efficacy of EB for this population. Therefore, this meta-analysis aims to investigate the effects of EB on chemotherapy-treated patients. Eight electronic databases were searched from their inception until February 15, 2024, to identify relevant studies. The inclusion and exclusion criteria were applied to filter the retrieved studies. Outcomes were various quantitative assessments. This systematic review was registered in the PROSPERO Registry (registration number CRD42023466630). Nine randomized controlled trials (RCTs) met eligibility criteria (n = 704). The meta-analysis results demonstrated that EB significantly reduced levels of anxiety and depression. Subgroup analysis revealed that the intervention frequency of 1 time/day had a greater effect on the improvement of negative emotions, compared with 2 times/day and 5 times/week. The intervention duration of 4weeks showed more efficacy in reducing depression scores than 12weeks or 16weeks; however, no statistical difference was observed for anxiety scores. EB exercise can reduce depression and anxiety symptoms in chemotherapy-treated patients. However, the results should be interpreted with caution as existing methodological limitations. The findings provided insights into the development of public health initiatives to improve the negative emotion among chemotherapy-treated patients by EB exercise.

Daidzein ameliorates peripheral neuropathy in Sprague Dawley rats.

Neuropathy is the most common disorder comprising peripheral nerve damage in diabetic patients. Prolonged hyperglycaemia and oxidative stress cause metabolic imbalance and are the key reasons for the development of diabetic neuropathy. Daidzein, a soy isoflavone possesses potent anti-hyperglycaemic and antioxidant activity. The present study aims to check the protective effect of Daidzein in diabetic neuropathy in rats. The experimental animal model involved induction of diabetes in rats by intraperitoneal injection of streptozotocin (55mg/kg). Following confirmation of diabetes, the diabetic rats were subjected to oral treatment with varying doses of Daidzein (25, 50, and 100mg/kg) and pregabalin (30mg/kg) for a duration of 4weeks, initiated 6weeks after diabetes induction. Results indicated that Daidzein treatment led to a significant reduction in plasma glucose levels and an improvement in body weight among diabetic animals. Moreover, Daidzein demonstrated a positive impact on sensory functions, as evidenced by the effect on tail withdrawal and response latency. Mechanical hyperalgesia and allodynia, common symptoms of diabetic neuropathy, were also significantly reduced with both Daidzein and pregabalin treatment. Notably, nerve conduction velocities exhibited improvement following the administration of Daidzein and pregabalin. Further investigation into the molecular mechanisms revealed that Daidzein treatment resulted in a notable enhancement of antioxidant enzyme levels and a reduction in the overexpression of NOX-4 in the sciatic nerve. This suggests that Daidzein's therapeutic effect is associated with the inhibition of oxidative stress via NOX-4. In summary, the findings of study suggests that, Daidzein treatment significantly attenuated diabetic neuropathy by inhibiting oxidative stress via NOX-4 inhibition.

The etiological profile of chronic organic non-bloody diarrhea in India: Emergence of inflammatory bowel disease as a dominant cause.

Chronic non-bloody diarrhea may be attributed either to functional or organic diseases. The latter category may present with malabsorption syndrome if there is extensive involvement of the small bowel, whereas diseases of the large bowel may only present with diarrhea sans malabsorption. Indian data has predominantly focussed on the etiological spectrum of malabsorption syndrome in adults. The primary aim of the current study was to evaluate etiological spectrum of chronic organic non-bloody diarrhea in India. This prospective observational study was done at a tertiary care hospital in North India. Patients ≥ 18years presenting with chronic non-bloody diarrhea of > 4weeks duration were enrolled in the study after exclusion of patients with IBS and anal incontinence. During the study period of 12months, 100 patients with chronic organic non-bloody diarrhea were evaluated. A definite etiological diagnosis was made in 97 patients (97%). The mean age of the patients was 48 ± 16.7years (58% males). The median duration of diarrhea was 5.5months (interquartile range [IQR] 3.5, 11). Inflammatory bowel disease (IBD) accounted for 45% of the cases making it the predominant cause for organic diarrhea. GI infections and adult-onset celiac disease accounted for 18% and 9% of the cases, respectively. Pancreatic disease, benign or neoplastic, accounted for 6% of the total cases. Notably, gastrointestinal (GI) malignancies manifesting as chronic non-bloody diarrhea were diagnosed in 5% of the patients. Our data suggests a paradigm shift in the etiological spectrum of chronic organic non-bloody diarrhea in India with the emergence of IBD as the predominant cause displacing GI infections.

Care in the Community: A COVID-19 initiative to reduce hospital re-presentations among community-dwelling people.

The COVID-19 pandemic has had a substantial impact on the utilisation of hospital and emergency department (ED) services. We examined the effect of a rapid response service on hospital re-presentations among people discharged from the ED and short-stay wards at a tertiary referral hospital. This retrospective cohort study compared 112 patients who completed the Care in the Community program with 112 randomly selected controls. Both cases and controls were discharged from hospital between September 2020 and June 2021. Intervention patients were evaluated by a multidisciplinary team, who implemented a goal-directed program of up to 4-weeks duration. Logistic regression, negative binomial regression and Cox proportional hazards regression were used to evaluate outcomes at 28 days and at 6 months. The median time between referral and the first home visit was 3.9 days. In adjusted analyses, the intervention reduced hospital re-presentations at 28 days (odds ratio: .40, 95% confidence interval (CI): .17-.94) and lengthened the time to the first hospital re-presentation (hazard ratio: .59, 95% CI: .38-.92). Although the intervention did not reduce the total number of hospital re-presentations at 6 months (adjusted incidence rate ratio: .73, 95% CI: .49-1.08), it reduced total time spent in hospital by 303 days (582 vs. 885). This study is among the first to investigate the effect of a community-based intervention on hospital re-presentations during the COVID-19 pandemic. It provides evidence that a sustainable 4-week intervention is associated with reduced hospital re-presentations and time spent in hospital.

Post-gastric sleeve gastrectomy mixed Wernicke's and Hashimoto's encephalopathies with brain atrophy: A case-report from Qatar

We present a case of a 21-year-old male patient who presented with progressive dizziness, gait instability, and ataxia of 1-week duration. Three months prior to presentation, the patient underwent Laparoscopic Sleeve Gastrectomy (LSG). His workup showed a very low level of thiamine, high thyroid-stimulating hormone (TSH) level, and very low free thyroxine (T4). The patient was diagnosed with Wernicke Encephalopathy (WE) post LSG, exacerbated by Hashimoto Encephalopathy (HE), given the history of an underlying uncontrolled Hashimoto's thyroiditis (HT).

Reliability of a Modified Watson-Jones Classification for Tibial Tubercle Fractures in Children.

The first case report describing a pediatric fracture of the tibial tubercle was published in 1852 in the Medical Times and Gazette, a Journal of Medical Science, literature, criticism, and news. A century later, in 1955, Sir Watson-Jones introduced the first classification system for this fracture. Despite the existence of several classification systems for pediatric tibial tubercle fractures in the medical literature, a crucial aspect of their validation-reliability and reproducibility-has not yet been systematically evaluated. In this study, a modified Watson-Jones (mWJ) classification system of tibial tubercle fractures in children was assessed for intraobserver and interobserver variability. Using the mWJ classification, 3 board-certified pediatric orthopaedic surgeons and 3 orthopaedic surgery residents, classified thirty tibial tubercle fractures based on anteroposterior and lateral radiographs on 2 separate occasions in a 2-week duration. Further comparison was made to evaluate the impact of advanced imaging, specifically computed tomography or magnetic resonance imaging, on diagnostic reliability and reproducibility. The study found substantial intraobserver reliability of the mWJ classification based on radiographs alone, with a Cohen weighted kappa (κ w ) coefficient of 0.733. When advanced imaging was utilized, the reliability of the classification improved to κ w = 0.783. Similarly, interobserver reliability demonstrated substantial consistency among observers when using radiographs alone (κ w = 0.69) and improved agreement with advanced imaging (κ w = 0.75). Notably, there was no significant difference in reliability scores between senior-level attendings and residents when analyzed as separate groups. Fracture classification systems are clinically relevant tools that help organize and transfer knowledge efficiently, provide treatment guidance, propose prognostic expectations, and improve communication in academic literature. The present study demonstrated substantial reproducibility of an mWJ fracture classification system both between and within individual surgeon raters. Level III-diagnostic.

Exploring protective potential of Vitamin E in mitigating liver steatosis in alcoholic liver injury.

Objective: To investigate and assess the efficacy of Vitamin E in preventing or reducing fatty liver changes associated with alcoholic liver injury. Study Design: Experimental study. Setting: Department of Anatomy and Animal Facility of Peshawar Medical College, Peshawar. Period: February 2018 to April 2020. Methods: The study involved eighteen male domestic rabbits (Oryctolagus cuniculus), organizing them into categories based on the time frames specified for the research. Animals in "Category E8" were subjected to an 8-week time period, while those in "Category E4" underwent a 4-week experimental duration. Each category was further divided into three groups: "Control Group A" received standard laboratory food and daily access to normal saline as drinking water, "Experimental Group B" received standard nutrition, a 30% ethanol solution in distal water (30ml per kg/day) and normal saline for drinking, and "Experimental Group C" was treated with the necessary standard diet, a 30% ethanol solution in distal water (30ml per kg/day), and "Vitamin E" (50mg dissolved in 2ml distal water per kg/day) via nasogastric tube. Liver tissue specimens from all animals were stained with H&amp;E and Masson’s trichrome stain for quantification of fatty change. Results: A significant difference in steatosis development was observed among the E4 groups and among the E8 groups having a respective p-values of 0.001 and 0.003. This underscored the impact of alcohol within the context of alcohol-induced liver injury. However, no appreciable differences were noted between BI &amp; CI and BII &amp; CII (p-values &gt; 0.05) indicating no significant distinction in liver steatosis between subjects treated with vitamin E and those not receiving vitamin E. Conclusion: In the context of alcohol-induced liver injury, the study failed to deliver anticipated protective benefits of vitamin E. There is a possibility of adverse effects, potentially rendering its use counterproductive.

Mini-invasive video thoracoscopic interventions in patients with acute pleural empyema

The use of video thoracoscopic interventions in patients with acute pleural empyema is gaining momentum in modern thoracic surgery. The need of determining the optimal timing of their implementation depending on the duration of the disease and the nature of changes in the parietal and visceral pleura remains open. The nature of changes in the parietal and visceral pleura of 249 patients with acute pleural empyema treated with video thoracoscopic interventions was evaluated. Patients were divided into 5 groups depending on the duration of the disease. It was determined that fibrinous accumulations in acute pleural empyema are replaced by cavity fragmenting formations after 6 weeks from the onset of the disease. The cessation of purulent exudate accumulation and the duration of pleural drainage after thoracoscopy depends on the duration of the disease at the time of thoracoscopy, as evidenced by the duration of pleural drainage in the period up to one month – 8 days from the onset of the disease, up to two months – 15 days, and after 8 weeks of duration – reached 20 days. The main indications for open surgical intervention in this group of patients were the failure of fractional lavage of the empyema cavity due to drainage or the impossibility of adequate rehabilitation according to the presence of a bronchopleural fistula with a duration of its existence of no more than 1 month and no tendency to closure. Inflammatory changes in the pleura in the form of fibrin deposits and cavity fragmentation in pleural empyema increase rapidly enough, the possibility of its effective rehabilitation during thoracoscopy without open surgical interventions is limited to 6 weeks from the onset of the disease. Keywords: acute purulent diseases of the pleura, minimally invasive surgical treatment, sanitation of the pleural cavity, duration of the disease.